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β-Amyloid activates nitric oxide synthesis and causes neuronal death in hippocampal astrocytes

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Digital fluorescence imaging was used to study the effects of the amyloid-beta peptide βA (full-length peptide, βA 1–42) and its neurotoxic fragment (βA 25–35) on nitric oxide (NO) synthesis and cell viability in mixed cultures of rat hippocampal neurons and astrocytes. It was found that both βA 1–42 and βA 25–35 stimulated NO synthesis in astrocytes, but not in neurons. L-NAME, an inhibitor of the inducible NO synthase, blocked the effect of βA on NO production almost completely, reduced βA-induced mitochondrial depolarization in astrocytes, and partly prevented neuronal death. The rate of NO synthesis was decreased in Ca2+-free medium, increased in the presence of antioxidants and the NADPH oxidase inhibitor, and decreased in the presence of the SH-reagent thimerosal.

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Abbreviations

βA:

β-amyloid

NO:

nitric oxide

TNFα:

tumor necrosis factor alpha

ROS:

reactive oxygen species

ΔΨm :

mitochondrial potential

Rh123:

rhodamine 123

L-NIL:

L-N6-(1-iminoethyl)-lysine

TEMPO:

2,2,6,6-tetramethylpiperidineoxy

DPI:

diphenylene iodonium chloride

DAF-fm:

4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate

IL1:

interleukin 1

iNOS:

inducible NO synthase

GSH:

glutathione (reduced)

NADPH:

nicotinamide dinucleotide phosphate reduced

PI:

propidium iodide

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    A. Yu. Abramov, V. A. Kasymov & V. P. Zinchenko

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  1. A. Yu. Abramov
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  2. V. A. Kasymov
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  3. V. P. Zinchenko
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Correspondence to V. P. Zinchenko.

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Original Russian Text © A.Yu. Abramov, V.A. Kasymov, V.P. Zinchenko, 2008, published in Biologicheskie Membrany, 2008, Vol. 25, No. 1, pp. 11–17.

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Abramov, A.Y., Kasymov, V.A. & Zinchenko, V.P. β-Amyloid activates nitric oxide synthesis and causes neuronal death in hippocampal astrocytes. Biochem. Moscow Suppl. Ser. A 2, 8–13 (2008). https://doi.org/10.1134/S1990747808010029

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  • DOI: https://doi.org/10.1134/S1990747808010029

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